The goal is to identify and map cancer susceptibility genes in man. Because of the paucity of genetic markers of high polymorphic information content for linkage analyses, we are presently focusing our efforts on the identification of new DNA polymorphisms, using Southern blotting methods. We are screening a cDNA library of "differentiation" genes (i.e., up-\or down-regulated by DMSO or phorbol esters) derived from HL60, a promyelogenous leukemia cell line. From 22 probes screened in the past year, we have identified 17 new polymorphisms. We are now characterizing each of these with regard to chromosomal mapping, Mendelian segregation, and allelic frequencies. We are also developing additional probes of genomic sequences that flank our original polymorphisms so as to allow haplotype identifications in later linkage analyses of cancer-prone pedigrees. (5)